Osteoclast lineage and function.

Osteoclasts are members of the monocyte/macrophage lineage and are formed by cellular fusions from their mononuclear precursors. Their differentiation is regulated by a number of other cells and their products, especially by RANKL and M-CSF. The resorbing osteoclasts are polarized and show specific plasma membrane domains. Polarization and bone resorption need a continuous membrane trafficking and modulation of the cytoskeleton. The most characteristic feature of osteoclasts is their unique capacity to dissolve crystalline hydroxyapatite by targeted secretion of HCl into the extracellular resorption lacuna. Organic matrix is degraded by enzymes like cathepsin K and the degradation products are transcytosed through the cell for secretion. Dissolution of hydroxyapatite releases large amounts of soluble calcium, phosphate and bicarbonate. Removal of these ions apparently involves the vesicular pathways and direct ion transport via different ion exchangers, channels and pumps. Detailed molecular knowledge of osteoclast differentiation and function has helped us to identify several target molecules and develop specific treatments to inhibit pathological bone resorption in various skeletal diseases.